LENGTH INCREASE OF THE SIDE-CHAIN OF IDOXIFENE DOES NOT IMPROVE ITS ANTAGONISTIC POTENCY IN BREAST-CANCER CELL-LINES

Linkage of specific residues onto steroidal estrogens through a long a liphatic side chain leads to ''pure antiestrogens'' devoid of residual estrogenic activity. Therefore, we assessed whether an increase in th e length of the side chain of the triphenylethylenic antiestrogen idox ifene might increase its antagonistic potency. Culture of MCF-7 and ta moxifen-resistant variant RTX6 cells in the presence of CB 7675, a (CH 2)(8) derivative of idoxifene [(CH2)(2)], ruled out this possibility. This compound partly blocked MCF-7 cell growth only at 10(-6) M to alm ost the same extent as tamoxifen and failed to inhibit the growth of R TX6 cells, whereas the pure antiestrogen RU 58 668 was effective on bo th cell lines at much lower concentration. This absence of improvement was reflected in the observation of an efficiency for down-regulating progesterone receptor no better than that of tamoxifen. Pure antiestr ogens are known to down-regulate the estrogen receptor, whereas triphe nylethylenic antiestrogens up-regulate the receptor; CB 7675 behaves a s the latter in agreement with its lack of strong antagonistic activit y.